書誌事項
- タイトル別名
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- RNA phase transition-induced Synucleinopathies in neurobiology and therapeutic strategy
抄録
<p>Aggregated α-synuclein (α-Syn) triggers development of synucleinopathies and it has also known that pathological α-Syn can propagate in the brain like as a prion protein. However, the molecular mechanisms remain unclear. We have recently reported that RNA G-quadruplex (G4RNA) initiates phase transition of fragile X tremor ataxia syndrome (FXTAS)-related prion-like proteins, resulting in neuronal dysfunction (Sci Adv. 2021). Here, we introduce α-Syn phase transition induced by G4RNA. α-Syn can bind to guanin-enriched RNA sequences in randomized RNA and specifically form a complex with G4RNAs, but not other RNAs. Purified α-Syn underwent liquid-liquid phase separation (LLPS), and liquid-to-solid transition of α-Syn was significantly facilitated by adding G4RNAs under the condition of molecular crowding. In addition, cellular stress markedly increased G4RNA levels and G4RNA assembly caused α-Syn aggregation in α-Syn-expressed cells. Moreover, we demonstrated that G4RNA is co-aggregated with phosphorylated α-Syn in dopaminergic neurons of the substantia nigra, and that G4 ligand attenuates α-Syn aggregation and propagation in α-Syn preformed fibril (PFF)-injected mice. These results suggest that G4RNA is a key factor for the onset of synucleinopathies, and propose a novel therapeutic approach.</p>
収録刊行物
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- 日本薬理学会年会要旨集
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日本薬理学会年会要旨集 95 (0), 1-S13-2-, 2022
公益社団法人 日本薬理学会
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キーワード
詳細情報 詳細情報について
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- CRID
- 1390291767688568320
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- ISSN
- 24354953
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- 本文言語コード
- ja
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- データソース種別
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- JaLC
- Crossref
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- 抄録ライセンスフラグ
- 使用不可